Treatment of Experimental Staphylococcus aureus Endocarditis: Comparison of Cephalothin, Cefazolin, and Methicillin

The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactamase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and one-eighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.     

Comparative evaluation of A-56619, A-56620, and nafcillin in the treatment of experimental Staphylococcus aureus osteomyelitis

A rabbit model for Staphylococcus aureus osteomyelitis was used to compare the results of treatment with A-56619 and A-56620, two new aryl-fluoroquinolones, and nafcillin. A-56619 (15 mg/kg) and A-56620 (20 mg/kg), both used for 28 days of treatment, were injected subcutaneously every 12 h, and nafcillin (40 mg/kg) was injected every 6 h. After treatment, S. aureus was found on bone marrow cultures from 19 of 20 control rabbits, 6 of 20 treated with A-56619, 14 of 20 treated with A-56620, and 8 of 20 treated with nafcillin. Drug concentrations in serum and uninfected and infected bone were measured 1 h after A-56619 and A-56620 injection and 30 min after nafcillin injection in a group of rabbits that had been infected for 3 to 4 weeks. The concentrations in infected bone were similar for all three drugs and were significantly higher than in uninfected bone. The results of this study showed that A-56619 had a high rate of eradication of S. aureus from infected bone and compared favorably to nafcillin.     

Integration of pharmacokinetics and pharmacodynamics of methicillin in curative treatment of experimental endocarditis

The rabbit model for Staphylococcus aureus endocarditis was used to compare cure rate and pharmacokinetic profile of four dosing regimens of methicillin. Equal daily doses (120 mg/kg) in five day treatment periods were given to 40 rabbits. Doses were given by bolus 20 mg/kg every 4 h (q 4 h), 40 mg/kg every 8 h (q 8 h), 60 mg/kg every 12 h (q 12 h) or by continuous infusion. The methicillin pharmacokinetics resulting from each regimen were monitored along with the course of the infection in each rabbit. For each regimen, time above MBC, peak height, area under the curve (AUC) above MIC and MBC were measured. Post antibiotic effect (PAE) duration and log growth time (LGT) values were obtained from the literature. Significantly more rabbits treated by q 4 h and q 8 h (P less than 0.05) survived 14 days after cessation of methicillin treatment than did rabbits treated q 12 h or continuous infusion. The four regimens differed in peak concentration and time above MBC. Despite producing the highest peak concentrations, the q 12 h regimen was the least effective. The duration above MBC was 2.0, 1.5, and 0.6 hours for q 12 h, q 8 h and q 4 h regimens, respectively. Continuous infusion produced methicillin concentration just above MBC over the entire five day treatment period, but was not as effective as q 4 h or q 8 h regimens. The most successful intermittent bolus regimens were those in which the sum of time above MBC, the duration of PAE, and one LGT were approximately equal to the actual dosage interval.     

Pharmacokinetics of intramuscular ceforanide in infants, children, and adolescents.

We studied the pharmacokinetics of intramuscular ceforanide in 46 infants, children, and adolescents, ranging in age from 1 month to 17 years. After the subjects were given 20-mg doses of ceforanide per kg, the mean peak plasma concentration was 56.3 microgram/ml (range, 27.0 to 95.0), the mean 8-h level was 5.9 microgram/ml (range, 1.5 to 13.5), and the mean 12-h level was 1.5 microgram/ml (range, 0.2 to 4.2). Ceforanide half-life varied with the ages of the patients: in 1- to 2-year-old children, in half-life was significantly shorter (1.5 h) than in younger or older children. Plasma concentrations at 8 and 12 h after a dose were lowest in 1- to 2-year-old children. There was no relationship between the area under the curve, the volume of distribution, or the body clearance of ceforanide to the ages of the patients. Within 6 h of administration of the drug, a mean of 77.5% of a dose was excreted in urine, and at the end of 12 h, virtually all (93.9%) of the administered dose was recovered in urine samples. The administration of ceforanide every 12 h did not result in drug accumulation. A dose of 20 mg of ceforanide per kg every 12 h is recommended for most pediatric patients. Dosage recommendations for 1- to 2 year-old children are presented.     

Pharmacokinetics of nafcillin in infants with low birth weights.

The pharmacokinetics of nafcillin were studied in 13 premature neonates with suspected sepsis. The mean weight of the infants studied was 1.19 kg (range, 0.73 to 2.21 kg). Infants less than 7 days of age were given 100 mg of nafcillin per kg per 24 h (every 12 h), and infants more than 7 days of age were given 100 mg of nafcillin per kg per 24 h (every 8 h). Blood samples were obtained before the first dose on day 3 of therapy and at 0.5, 1.5, 3, and 6 h thereafter. Nafcillin concentrations were measured by a microbiological assay. A mean volume of distribution of 326 ml/kg and an elimination rate constant of 0.2040 h-1 were obtained in 10 patients less than 21 days of age. Three patients from 24 to 68 days of age had a mean volume of distribution of 303 ml/min and a mean elimination rate constant of 0.3944 h-1 (P less than 0.05). These data suggest that doses of nafcillin lower than those currently recommended may be adequate to achieve desired peak plasma levels of approximately 75 microgram/ml in infants with low birth weights.     

Induction of beta-lactamase and methicillin resistance in unusual strains of methicillin-resistant Staphylococcus aureus

Two unusual, heterogeneously-resistant, strains of Staphylococcus aureus appeared resistant to oxacillin, but susceptible to methicillin by disc diffusion methods. In agar dilution tests, both strains were oxacillin-resistant. One was susceptible to methicillin, and the other gave a paradoxical reaction, with growth only on plates containing low (0.5, 1 and 2 mg/l) and high (32 and 64 mg/l) concentrations of antibiotic. Induction of methicillin resistance was tested by inoculating each strain on to agar plates containing an inhibitory concentration of methicillin (8 mg/l), and then placing discs containing inducers (oxacillin, nafcillin, methicillin and CBAP [2-(2'-carboxyphenyl) benzoyl-6-aminopenicillanic acid]) on the agar surface. Colonies grew only around discs containing effective inducers. Oxacillin and CBAP were much more potent inducers of methicillin resistance and beta-lactamase than was nafcillin or methicillin. These data suggest that the mechanism that regulates induction of the low-affinity penicillin binding protein (PBP-2') may be altered in these strains. Similar mechanisms appear to induce both beta-lactamase and methicillin resistance.     

Effectiveness of Nafcillin, Methicillin, and Cephalothin in Experimental Staphylococcus aureus Endocarditis

Nafcillin, methicillin, and cephalothin (40 mg/kg every 6 h) were all effective in reducing the number of Staphylococcus aureus in vegetations in rabbits with endocarditis. Nafcillin and methicillin reduced the number of S. aureus at a significantly faster rate than did cephalothin. Nafcillin and methicillin also reduced titers of the S. aureus more rapidly than did cephalothin in vitro, both in broth and in rabbit serum.     

Nafcillin Treatment of Staphylococcus aureus Meningitis

Serial serum and cerebrospinal fluid nafcillin concentrations were determined in a patient successfully treated with nafcillin (200 mg/kg per day) for Staphylococcus aureus bacteremia and meningitis. Nafcillin and methicillin cerebrospinal fluid concentrations were compared.     

Pharmacokinetics and cerebrospinal fluid concentration of nafcillin in pediatric patients undergoing cerebrospinal fluid shunt placement

Postoperative infection is among the most common complications in patients with cerebrospinal fluid shunt placement. Nafcillin is often used for prophylaxis but not pharmacokinetic data are available perioperatively in pediatric patients. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal concentrations of nafcillin. Ten patients (mean age 8.0 +/- 5.6 years) received three doses of intravenous nafcillin, 50 mg/kg every 6 h; the first dose was administered 1 h prior to surgery. Multiple blood samples were collected during and after surgery and the cerebrospinal fluid sample was obtained at the time of shunt insertion. Urine samples were collected for 24 h after initiation of nafcillin. Nafcillin was analyzed with an HLPC method. The peak serum concentrations ranged from 22 to 107 micrograms/ml; cerebrospinal fluid concentrations ranged from 0.02 to 0.30 (mean 0.16 +/- 0.11) micrograms/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.90 +/- 0.55 l/kg/h, 0.12 +/- 0.04 l/kg/h, 0.70 +/- 0.52 l/kg, and 0.5 +/- 0.1 h, respectively. 16% of total nafcillin dose was excreted in the urine. A 4-fold variability in total clearance and a 10-fold variation in cerebrospinal fluid concentrations of nafcillin was observed in these patients. Further, the concentrations of nafcillin attained in the cerebrospinal do not appear to be adequate, based on its minimum inhibitory concentration of 0.5 micrograms/ml against very susceptible staphylococci. These data, in addition to the fact that an increasing number of staphylococci are becoming resistant to nafcillin, question the usefulness of prophylactic nafcillin in pediatric patients undergoing shunt procedures.     

Cefoperazone treatment of experimental endocarditis

Cefoperazone (10 mg/kg) and cephalothin (20 mg/kg) administered intramuscularly every 6 h were both effective in reducing the number of Staphylococcus aureus cells in vegetations in rabbits with endocarditis. Cefoperazone produced higher peak concentrations and greater bactericidal activity in serum than did cephalothin. Cefoperazone (40 mg/kg) administered every 6 h was significantly more effective than cefamandole (40 mg/kg) administered every 6 h in reducing the number of Enterobacter aerogenes cells in vegetations. Although cefamandole produced higher peak concentrations in serum, the serum bactericidal activity was greater with cefoperazone. The half-lives in serum were 0.64 h for cefoperazone and 0.46 h for cephalothin and cefamandole.     

Comparative In Vitro Activity of Nafcillin, Oxacillin, and Methicillin in Combination with Gentamicin and Tobramycin Against Enterococci

The in vitro activity of nafcillin, oxacillin, and methicillin alone and in combination with gentamicin and tobramycin against 30 strains of enterococci was investigated. The penicillinase-resistant penicillins were less active than penicillin and ampicillin against the enterococci. Nafcillin was more active than oxacillin and methicillin. Sixty-six percent of strains were inhibited by nafcillin at 6.25 μg/ml, but none was inhibited by oxacillin and methicillin at the same concentration. At 12.5 μg/ml, 83, 16, and 0% were inhibited by nafcillin, oxacillin, and methicillin, respectively. By using a variety of criteria and analyses, it was shown that none of the antibiotic combinations studied demonstrated enhanced killing of all strains of enterococci. Nafcillin-gentamicin was the best combination, and enhanced killing was demonstrated against most strains. Oxacillin was more effective than methicillin when combined with gentamicin. Tobramycin was probably less effective than gentamicin in combination with the penicillinase-resistant penicillins against enterococci.     

Cefadroxil kinetics and dynamics in a pediatric patient with acute osteomyelitis

Cefadroxil has been used for the treatment of acute osteomyelitis. However, its pharmacokinetics and pharmacodynamics have not been studied in these patients. We evaluated the kinetics and dynamics of cefadroxil in a pediatric patient with osteomyelitis caused by Staphylococcus aureus. After initial clinical improvement on intravenous nafcillin, the patient received oral cefadroxil, 60 mg/kg every 12 h. Blood samples were collected at 0, 1, 2, 4, 6, 8 and 12 h; bactericidal titers were determined at 2 and 12 h. Cefadroxil was measured by an HPLC method. The peak and trough serum concentration of cefadroxil was 35.4 and 0.5 micrograms/ml, respectively. The oral clearance and elimination half-life were 11.5 ml/min/kg and 2.4 h, respectively. The peak bactericidal titer was 1:4 and the trough titer was less than 1:2 for the infecting organism. The child's finger appeared worse with an increase in swelling and erythema after 2 days of cefadroxil therapy. Cefadroxil was discontinued and the patient was treated successfully with intravenous nafcillin. The apparent failure of cefadroxil therapy can be explained by lower than recommended peak (greater than or equal to 1:8) and trough (greater than or equal to 1:2) titers for therapeutic success. Thus, an alternative dosage regimen of cefadroxil should be considered in the future studies.     

Comparative Activities of Telavancin Combined with Nafcillin,Imipenem, and Gentamicin against Staphylococcus aureus

Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.     

Efficacy of Ceftriaxone and Gentamicin Given Once a Day by Using Human-Like Pharmacokinetics in Treatment of Experimental Staphylococcal Endocarditis

We compared the efficacy of ceftriaxone combined with gentamicin, both given once a day, with that of cloxacillin given every 4 h plus gentamicin given once a day or in three daily doses (t.i.d.) for the treatment of experimental methicillin-susceptible staphylococcal endocarditis. The antibiotics were administered by using human-like (H-L) pharmacokinetics that simulated the profiles of these drugs in human serum. Animals with catheter-induced endocarditis were infected intravenously with 10(5) CFU of Staphylococcus aureus S5 (MICs and minimal bactericidal concentrations of cloxacillin, ceftriaxone, and gentamicin, 0.5 and 2 microg/ml, 4 and 8 microg/ml, and 0.5 and 1 microg/ml, respectively). The animals were then treated for 24 h with cloxacillin at a dose of 2 g that simulated H-L pharmacokinetics (H-L 2 g) every 4 h alone or combined with gentamicin (administered at doses of H-L 1 mg/kg of body weight every 8 h or H-L 4.5 mg/kg every 24 h) or with ceftriaxone at H-L 2 g every 24 h alone or combined with gentamicin (administered at doses of H-L 1 mg/kg every 8 h or H-L 4.5 mg/kg every 24 h). The results of therapy for experimental endocarditis due to the S5 strain showed that (i) cloxacillin alone is more effective than ceftriaxone alone in reducing the bacterial load (P < 0.01), (ii) the combination of cloxacillin or ceftriaxone with gentamicin is more effective than each of these drugs alone (P < 0.01), and (iii) Ceftriaxone H-L plus gentamicin H-L 4.5 mg/kg, both administered every 24 h, showed efficacy similar to that of the "gold standard," cloxacillin H-L plus gentamicin H-L 1 mg/kg t.i.d. (P > 0.05). An increase in the interval of administration of gentamicin to once daily resulted in a reduction in the numbers of bacteria in the vegetations equivalent to that achieved with the recommended regimen of cloxacillin plus gentamicin t.i.d. in the treatment of experimental endocarditis due to methicillin-susceptible S. aureus. Ceftriaxone plus gentamicin, both administered once a day, may be useful for home-based therapy for selected cases of staphylococcal endocarditis.     

Clindamycin therapy of experimental Staphylococcus aureus endocarditis.

The efficacy of clindamycin in the treatment of experimental endocarditis in rabbits was compared with that of nafcillin. Both drugs were administered intramuscularly three times daily for 5 days, clindamycin at doses of 6.25, 12.5, 25, or 50 mg/kg and nafcillin at a dose of 200 mg/kg. The minimum inhibitory and bactericidal concentrations (0.125 microgram/ml) of clindamycin for the test strain of Staphylococcus aureus were very similar to the corresponding concentrations (0.25 microgram/ml) of nafcillin. The effectiveness of clindamycin against the experimental endocarditis was dose dependent. The therapeutic accomplishments of the two highest clindamycin doses were equivalent to those attained with 200 mg of nafcillin per kg. The rates of sterilization of vegetations were equal when the serum bactericidal titers of these drugs were greater than or equal to 1:8. In special situations the administration of clindamycin in high doses could prove useful in the treatment of S. aureus endocarditis.     

Ranitidine prophylaxis in acute gastric mucosal damage in critically ill pediatric patients

We determined the ranitidine dosage necessary to maintain gastric pH at or above 4 in 40 critically ill children. The patients were divided into four groups of ten patients each. They were treated with ranitidine in the following dosages: a) 2 mg/kg by NG tube every 12 h; b) 4 mg/kg by NG tube every 12 h; c) 0.75 mg/kg iv every 6 h; d) 1.5 mg/kg iv every 6 h. The fourth group had a higher median pH than the other groups, in spite of also having the highest risk of acute gastric mucosal damage (AGMD). Eight (80%) of ten patients in the fourth group had a pH greater than or equal to 4 or more than 80% of the study period. We recommend 1.5 mg/kg iv every 6 h for gastric acid inhibition in AGMD prophylaxis in children.     

Ceforanide and cefazolin therapy of pneumonia: comparative clinical trial

Ceforanide is a new (parenteral) long-acting cephalosporin with antimicrobial activity comparable to those of other second-generation cephalosporins. In a randomized prospective study, patients with community-acquired bacterial pneumonia were treated with ceforanide at 0.5 g every 12 h (28 cases) or with cefazolin at 1.0 g every 8 h (26 cases). The study groups were comparable in clinical and laboratory findings, including etiological diagnosis. Streptococcus pneumoniae was isolated from the sputum of 38 patients, of whom 8 (21%) were bacteremic. Mean peak and trough serum levels of ceforanide drawn 1 and 11.5 h after the 0.5-g intravenous dose were 39.6 and 2.5 microgram/ml, respectively. Of the 50 patients evaluable for efficacy, all responded clinically with no serious adverse reactions. In spite of clinical improvement and in vitro susceptibility, Haemophilus influenzae persisted in the sputum of five of the eight cefazolin-treated patients and four of the five patients treated with ceforanide. Ceforanide appears to be as safe and effective as cefazolin for the therapy of pneumonia caused by S. pneumoniae or H. influenzae, but neither drug was effective in clearing H. influenzae from the sputum.     

Efficacy of teicoplanin-gentamicin given once a day on the basis of pharmacokinetics in humans for treatment of enterococcal experimental endocarditis

With the aim of investigating home therapy for enterococcal endocarditis, we compared the efficacy of teicoplanin combined with gentamicin given once a day or in three daily doses (t.i.d.) with the standard treatment, ampicillin plus gentamicin administered t.i.d., for treating experimental enterococcal endocarditis. The antibiotics were administered by using "human-like pharmacokinetics" (H-L), i.e, pharmacokinetics like those in humans, that simulated the profiles of these drugs in human serum. Animals with catheter-induced endocarditis were infected intravenously with 10(8) CFU of Enterococcus faecalis EF91 (MICs and MBCs of ampicillin, gentamicin, and teicoplanin, 0.5 and 32, 16 and 32, and 0.5 and 1 microg/ml, respectively) and were treated for 3 days with ampicillin H-L at 2 g every 4 h plus gentamicin H-L at 1 mg/kg every 8 h, or teicoplanin H-L at 10 mg/kg every 24 h, alone or combined with gentamicin, administered at dose of H-L at 1 mg/kg every 8 h or H-L at 4.5 mg/kg every 24 h. The results of therapy for experimental endocarditis due to EF91 showed that teicoplanin alone was as effective as ampicillin alone in reducing the bacterial load (P > 0.05). The combination of ampicillin or teicoplanin with gentamicin was more effective than the administration of both drugs alone in reducing the log(10)CFU/gram of aortic vegetation (P < 0.01 and P < 0.05, respectively). Teicoplanin plus gentamicin H-L at 4.5 mg/kg, both administered every 24 h, showed an efficacy equal to the "gold standard," ampicillin plus gentamicin H-L at 1 mg/kg t.i.d. (P > 0.05). Increasing the interval of administration of gentamicin to a single daily dose combined with teicoplanin resulted in a reduction of bacteria in the vegetations equivalent to that achieved with the recommended regimen of ampicillin plus thrice-daily gentamicin in the treatment of experimental endocarditis due to E. faecalis. Teicoplanin plus gentamicin, both administered once a day, may be useful home therapy for selected cases of enterococcal endocarditis.     

Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration

We conducted a multicenter study of the safety, tolerability, and plasma pharmacokinetics of the parenteral formulation of voriconazole in immunocompromised pediatric patients (2 to 11 years old). Single doses of 3 or 4 mg/kg of body weight were administered to six and five children, respectively. In the multiple-dose study, 28 patients received loading doses of 6 mg/kg every 12 h on day 1, followed by 3 mg/kg every 12 h on day 2 to day 4 and 4 mg/kg every 12 h on day 4 to day 8. Standard population pharmacokinetic approaches and generalized additive modeling were used to construct the structural pharmacokinetic and covariate models used in this analysis. In contrast to that in adult healthy volunteers, elimination of voriconazole was linear in children following doses of 3 and 4 mg/kg every 12 h. Body weight was more influential than age in accounting for the observed variability in voriconazole pharmacokinetics. Elimination capacity correlated with the CYP2C19 genotype. Exposures were similar at 4 mg/kg every 12 h in children (median area under the concentration-time curve (AUC), 14,227 ng. h/ml) and 3 mg/kg in adults (median AUC, 13,855 ng. h/ml). Visual disturbances occurred in 5 (12.8%) of the 39 patients and were the only drug-related adverse events that occurred more than once. No withdrawals from the study were related to voriconazole. We conclude that pediatric patients have a higher capacity for elimination of voriconazole per kilogram of body weight than do adult healthy volunteers and that dosages of 4 mg/kg may be required in children to achieve exposures consistent with those in adults following dosages of 3 mg/kg.     

Enoxacin compared with vancomycin for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis.

Enoxacin administered orally was compared with vancomycin administered intravenously for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis. The MICs and MBCs of both enoxacin and vancomycin for an inoculum of 5.0 X 10(5) CFU of the methicillin-resistant S. aureus strain per ml were 1.56 microgram/ml. With an inoculum of 10(8) CFU/ml, enoxacin at 6 micrograms/ml and vancomycin at 180 micrograms/ml resulted in similar decreases in numbers of methicillin-resistant S. aureus in broth. Methicillin-resistant S. aureus endocarditis in rabbits was treated with enoxacin at 100 mg/kg orally every 12 h or vancomycin at 30 mg/kg intravenously every 12 h for 3 or 5 days. Enoxacin treatment for 3 or 5 days and vancomycin treatment for 5 days significantly reduced bacterial counts of vegetations compared with those in untreated control rabbits after 1 day of infection. Bacterial counts of vegetations after vancomycin treatment for 3 days did not differ significantly from those of untreated controls. Bacterial counts of vegetations in the four therapeutic groups did not differ significantly from one another. In uninfected rabbits single doses of vancomycin at 30 mg/kg administered intravenously achieved much higher concentrations in serum than did single doses of enoxacin at 100 mg/kg administered orally. Enoxacin had an elimination half-life in serum that was approximately 1.5 times longer than that of vancomycin. This study demonstrated that enoxacin administered orally is as effective as vancomycin administered intravenously for the treatment of experimental methicillin-resistant S. aureus endocarditis.